1. IN THE NAME OF GOD
GI CANCER

2. GASTRIC CARCINOMA Incidence and Epidemiology
The second most frequent cause of worldwide cancer-related death
The mortality rate dropped in men and women
Although the incidence of gastric cancer has decreased worldwide, it remains high in such disparate geographic regions as Japan, China, Chile, and Ireland.

3. Risk factors : lower socioeconomic classes ,Migrants from high- to low-incidence nations maintain their susceptibility to gastric cancer, whereas the risk for their offspring approximates that of the new homeland
These findings suggest that an environmental exposure, probably beginning early in life, with dietary carcinogens considered the most likely factor(s)

4. Pathology
85% adenocarcinomas, 15% due to lymphomas, gastrointestinal stromal tumors (GISTs), and leiomyosarcomas
Gastric adenocarcinomas may be subdivided into two categories:
Diffuse type, cell cohesion is absent, so that individual cells infiltrate and thicken the stomach wall without forming a discrete mass
Intestinal type, cohesive neoplastic cells that form gland like tubular structures

5. The diffuse carcinomas :younger patients, develop throughout the stomach (including the cardia), result in a loss of distensibility of the gastric wall (so- called linitis plastica, or “leather bottle” appearance), and carry a poorer prognosis
Diffuse cancers have defective intercellular adhesion, mainly as a consequence of loss of expression of E-cadherin.

6. Intestinal-type lesions are frequently ulcerative, more commonly appear in the antrum and lesser curvature of the stomach, and are often preceded by a prolonged precancerous process, often initiated by H. pylori infection
Incidence of diffuse carcinomas is similar in most populations
Intestinal type tends to predominate in the high-risk geographic regions and is less likely to be found in areas where the frequency of gastric cancer is declining

7. In United States, ∼30% of gastric cancers originate in the distal stomach, ∼20% arise in the midportion of the stomach, and ∼40% originate in the proximal third of the stomach
The remaining 10% involve the entire stomach

8. Etiology
The long-term ingestion of dried, smoked, and salted foods … high concentrations of nitrates …. bacteria … nitrites(carcinogen)
Such bacteria may be introduced exogenously through the ingestion of partially decayed foods, which are consumed in abundance worldwide by the lower socioeconomic classes

9. Bacteria such as H. pylori may also contribute to this effect by causing chronic inflammatory atrophic gastritis, loss of gastric acidity, and bacterial growth in the stomachs
Although the risk for developing gastric cancer is thought to be sixfold higher in people infected with H. pylori, it remains uncertain whether eradicating the bacteria after infection has already occurred actually reduces this risk

10. Loss of acidity :acid-producing cells of the gastric antrum removed surgically to control benign peptic ulcer disease or when achlorhydria, atrophic gastritis, and even pernicious anemia develop in the elderly
Serial endoscopic in patients with atrophic gastritis have documented replacement of the usual gastric mucosa by intestinal type cells(IM) …. cellular atypia and eventual neoplasia

11. H. pylori has not been associated with the diffuse, more proximal form of gastric carcinoma or with cancers arising at the gastroesophageal junction or in the distal esophagus
Approximately 10–15% of adenocarcinomas appearing in the proximal stomach, the gastroesophageal junction, and the distal esophagus overexpress the HER2/neu gene …. benefit from treatment directed against this target (i.e., trastuzumab [Herceptin]).

12. Several additional etiologic factors :
Gastric ulcers and adenomatous polyps(but data are unconvincing)
Extreme hypertrophy of gastric rugal folds (i.e., Menetrier’s disease)giving the impression of polypoid lesions, has been associated with a striking frequency of malignant transformation

13. Blood group A have a higher incidence than blood group O ……
Blood group A have a higher incidence than blood group O ……. related to differences in the mucous secretion, leading to altered mucosal protection from carcinogens
A germline mutation in the E-cadherin gene (CDH1), autosomal dominant … coding for a cell adhesion protein, high incidence of occult diffuse-type gastric cancers in young asymptomatic carriers
Duodenal ulcers are not associated with gastric cancer

15. Clinical Features
Gastric cancers, when superficial and surgically curable, usually produce no symptoms
As the tumor becomes more extensive, patients may complain of an insidious upper abdominal discomfort varying in intensity from a vague, postprandial fullness to a severe, steady pain
Anorexia, often with slight nausea, is very common but is not the usual presenting complaint

16. Weight loss , and nausea and vomiting are particularly prominent in patients whose tumors involve the pylorus; dysphagia and early satiety may be the major symptoms caused by diffuse lesions originating in the cardia
There may be no early physical signs
A palpable abdominal mass indicates long-standing growth and predicts regional extension

17. Gastric carcinomas spread by direct extension through the gastric wall to the perigastric tissues, occasionally adhering to adjacent organs such as the pancreas, colon, or liver
The disease also spreads via lymphatics or by seeding of peritoneal surfaces

18. Metastases to intraabdominal and supraclavicular lymph nodes occur frequently, as do metastatic nodules to the ovary (Krukenberg’s tumor), periumbilical region (“Sister Mary Joseph node”), or peritoneal cul-de-sac (Blumer’s shelf palpable on rectal or vaginal examination); malignant ascites may also develop
The liver is the most common site for hematogenous spread of tumor

19. IDA in men and of occult blood in the stool in both sexes mandates a search for an occult gastrointestinal tract lesion
A careful assessment is of particular importance in patients with atrophic gastritis or pernicious anemia
Unusual clinical features : migratory thrombophlebitis, microangiopathic hemolytic anemia, diffuse seborrheic keratoses (so-called Leser-Trelat sign), and acanthosis nigricans

20. Diagnosis
Double-contrast radiographic , esophagogastroscopy and CT scanning for the evaluation of patients with epigastric complaints
Gastric ulcers identified at the time of such endoscopic procedure may appear benign but merit biopsy in order to exclude a malignancy

21. Malignant gastric ulcers must be recognized before they penetrate into surrounding tissues, because the rate of cure of early lesions limited to the mucosa or submucosa is >80%
Because gastric carcinomas are difficult to distinguish clinically or endoscopically from gastric lymphomas, endoscopic biopsies should be made as deeply as possible, due to the submucosal location of lymphoid tumors

22. PRIMARY GASTRIC LYMPHOMA
Primary lymphoma of the stomach is relatively uncommon, accounting for <15% of gastric malignancies and ∼2% of all lymphomas
The stomach is the most frequent extranodal site for lymphoma, and gastric lymphoma has increased in frequency during the past 35 years

23. The disease is difficult to distinguish clinically from gastric adenocarcinoma; both tumors are most often detected during the sixth decade of life; present with epigastric pain, early satiety, and generalized fatigue; and are usually characterized by ulcerations with a ragged, thickened mucosal pattern demonstrated by contrast radiographs or endoscopic appearance

24. Diagnosis
be made through cytologic brushings of the gastric mucosa but usually requires a biopsy at gastroscopy or laparotomy
Failure of gastroscopic biopsies to detect lymphoma in a given case should not be interpreted as being conclusive, because superficial biopsies may miss the deeper lymphoid infiltrate
The macroscopic pathology of gastric lymphoma may also mimic adenocarcinoma, consisting of either a bulky ulcerated lesion localized in the corpus or antrum or a diffuse process spreading throughout the entire gastric submucosa and even extending into the duodenum

25. Microscopically, the vast majority of gastric lymphoid tumors are lymphomas of B-cell origin
Histologically, these tumors may range from well- differentiated, superficial processes (mucosa- associated lymphoid tissue [MALT]) to high-grade, large-cell lymphomas

26. Like gastric adenocarcinoma, infection with H
Like gastric adenocarcinoma, infection with H. pylori increases the risk for gastric lymphoma in general and MALT lymphomas in particular
Large cell lymphomas of the stomach spread initially to regional lymph nodes (often to Waldeyer’s ring) and may then disseminate

27. GASTRIC (NONLYMPHOID) SARCOMA
Leiomyosarcomas and GISTs make up 1–3% of gastric neoplasms.
They most frequently involve the anterior and posterior walls of the gastric fundus and often ulcerate and bleed
Even those lesions that appear benign on histologic examination may behave in a malignant fashion
These tumors rarely invade adjacent viscera and characteristically do not metastasize to lymph nodes, but they may spread to the liver and lungs

28. The treatment of choice is surgical resection.
Combination chemotherapy should be reserved for patients with metastatic disease
All such tumors should be analyzed for a mutation in the c-kit receptor…. responsive GISTs to imatinib mesylate (Gleevec) a selective inhibitor of the c-kit tyrosine kinase